A large-scale binding and functional map of human RNA-binding proteins

Eric L. Nostrand, Peter Freese, Gabriel A. Pratt, Xiaofeng Wang, Xintao Wei, Rui Xiao, Steven M. Blue, Jia-Yu Chen, Neal A. L. Cody, Daniel Dominguez, Sara Olson, Balaji Sundararaman, Lijun Zhan, Cassandra Bazile, Louis Philip Benoit Bouvrette, Julie Bergalet, Michael O. Duff, Keri E. Garcia, Chelsea Gelboin-Burkhart, Myles Hochman, Nicole J. Lambert, Hairi Li, Michael P. McGurk, Thai B. Nguyen, Tsultrim Palden, Ines Rabano, Shashank Sathe, Rebecca Stanton, Amanda Su, Ruth Wang, Brian A. Yee, Bing Zhou, Ashley L. Louie, Stefan Aigner, Xiang-Dong Fu (), Eric Lécuyer (), Christopher B. Burge (), Brenton R. Graveley () and Gene W. Yeo ()
Additional contact information
Eric L. Nostrand: University of California San Diego
Peter Freese: Massachusetts Institute of Technology
Gabriel A. Pratt: University of California San Diego
Xiaofeng Wang: Institut de Recherches Cliniques de Montréal (IRCM)
Xintao Wei: Institute for Systems Genomics, UConn Health
Rui Xiao: University of California San Diego
Steven M. Blue: University of California San Diego
Jia-Yu Chen: University of California San Diego
Neal A. L. Cody: Institut de Recherches Cliniques de Montréal (IRCM)
Daniel Dominguez: Massachusetts Institute of Technology
Sara Olson: Institute for Systems Genomics, UConn Health
Balaji Sundararaman: University of California San Diego
Lijun Zhan: Institute for Systems Genomics, UConn Health
Cassandra Bazile: Massachusetts Institute of Technology
Louis Philip Benoit Bouvrette: Institut de Recherches Cliniques de Montréal (IRCM)
Julie Bergalet: Institut de Recherches Cliniques de Montréal (IRCM)
Michael O. Duff: Institute for Systems Genomics, UConn Health
Keri E. Garcia: University of California San Diego
Chelsea Gelboin-Burkhart: University of California San Diego
Myles Hochman: Massachusetts Institute of Technology
Nicole J. Lambert: Massachusetts Institute of Technology
Hairi Li: University of California San Diego
Michael P. McGurk: Massachusetts Institute of Technology
Thai B. Nguyen: University of California San Diego
Tsultrim Palden: Massachusetts Institute of Technology
Ines Rabano: University of California San Diego
Shashank Sathe: University of California San Diego
Rebecca Stanton: University of California San Diego
Amanda Su: Massachusetts Institute of Technology
Ruth Wang: University of California San Diego
Brian A. Yee: University of California San Diego
Bing Zhou: University of California San Diego
Ashley L. Louie: University of California San Diego
Stefan Aigner: University of California San Diego
Xiang-Dong Fu: University of California San Diego
Eric Lécuyer: Institut de Recherches Cliniques de Montréal (IRCM)
Christopher B. Burge: Massachusetts Institute of Technology
Brenton R. Graveley: Institute for Systems Genomics, UConn Health
Gene W. Yeo: University of California San Diego

Nature, 2020, vol. 583, issue 7818, 711-719

Abstract: Abstract Many proteins regulate the expression of genes by binding to specific regions encoded in the genome1. Here we introduce a new data set of RNA elements in the human genome that are recognized by RNA-binding proteins (RBPs), generated as part of the Encyclopedia of DNA Elements (ENCODE) project phase III. This class of regulatory elements functions only when transcribed into RNA, as they serve as the binding sites for RBPs that control post-transcriptional processes such as splicing, cleavage and polyadenylation, and the editing, localization, stability and translation of mRNAs. We describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. Integrative analyses using five assays identify RBP binding sites on RNA and chromatin in vivo, the in vitro binding preferences of RBPs, the function of RBP binding sites and the subcellular localization of RBPs, producing 1,223 replicated data sets for 356 RBPs. We describe the spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization. These data expand the catalogue of functional elements encoded in the human genome by the addition of a large set of elements that function at the RNA level by interacting with RBPs.

Date: 2020
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DOI: 10.1038/s41586-020-2077-3

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